Presbycusis or age-related hearing loss is a complex disorder affecting 30 percent of the United States population aged 65 to 74 years, and at least 50 percent of the population 75 years of age and older. Slow deterioration of auditory function manifests itself through deficits in speech comprehension, especially in noisy environments. Inability to process speech is a contributing factor leading to a tendency of elderly individuals to withdraw from active participation in society. Studies in central auditory structures have found that inhibitory neurotransmitters are critically involved in determination of the frequency response area, control of dynamic range, detection of signals in noise, localization of sound in space and echo suppression. Proper coding of these signals may be vulnerable to the aging process. Studies completed during the previous grant period found significant age-related changes related to glycinergic neurotransmission in the dorsal cochlear nucleus and in the subunit makeup and pharmacology of the GABAA receptor in the inferior colliculus. Aging can be thought of, in part, as a slow progressive peripheral deafferentation. Similar to findings in the central auditory pathway of aged animals, noise trauma studies and animals with traumatized ears show significant plasticity in auditory cortex suggestive of a down regulation of GABA function. Proposed studies will examine age-related changes in the role of the inhibitory neurotransmitter GABA in primary auditory cortex (A1). Preliminary data are suggestive of layer specific, age-related, pre- and postsynaptic GABA changes in A1 consistent with altered GABA function. Proposed studies will characterize layer-specific, age-related changes in the presence of the synthetic enzyme for GABA, the subunit makeup, and the pharmacology of A1 GABAA receptors. Single unit studies will examine layer-specific, age-related changes in the response properties of A1 neurons and changes in their responses to GABAA antagonists and subunit selective agents. We expect to find layer-specific molecular and neurochemical changes reflected in the response properties and pharmacology of A1 neurons. Collectively, these studies should help characterize the impact of aging on inhibitory circuits in the A1. Understanding the function and the makeup of the aged GABAA receptor could lead to the development of selective pharmacotherapy for a subset of presbycusic individuals.